The present invention relates to a method for alleviating emesis associated with the administration of chemotherapeutic agents.
In cancer chemotherapy, violent emesis often interferes with acceptance of the therapy by the patient. This is particularly true in administering platinum compounds such as cisplatin (cis-dichlorodiamine platinum II) but it is also true in administering other chemotherapeutic agents such as dacarbazine, cyclophosphamide and doxorubicin.
With the exception of metoclopramide, standard antiemetics have been of little value in treating emesis in cancer therapy. U.S. Pat. No. 4,536,386 to Keenan discloses that metoclopramide has been effective in alleviating emesis caused by cisplatin when it is administered in very high dosages beginning prior to cisplatin administration and continuing through post administration.
A critical drawback in administering common anti-emetics, including metoclopramide, in treating the emesis associated with chemotherapy is that many benzamide-type antiemetic agents possess dopamine receptor antagonist activity. In pharmacological studies they block both apomorphine stereotypy and emesis. Consequently, certain effects related to blockade of central dopamine receptors, including extrapyramidal side effects, can accompany the administration of these drugs. This makes the drugs less desirable for use in conjunction with chemotherapy in which they are often administered in high dosages over prolonged periods of time. Many patients prefer to suffer emesis instead of the side effects attributed to the antiemetic agent. This is particularly true after one or two days of chemotherapy when emesis is less severe.